Process for the preparation of a propenal intermediate and derivatives thereof

A process for the preparation of (E)-N-(4-(4-fluorophenyl)-6-isopropyl-5-(3-oxoprop-1-enyl)pyrimidin-2-yl)-N-methylmethanesulfonamide of formula I which comprises:

• (a) Treating N-(4-(4-fluorophenyl)-5-formyl-6-isopropylpyrimidin-2-yl)-N-methyl methane-sulfonamide of formula III
• with a compound selected from
• i) an unsaturated compound of formula IV
• wherein R1 and R2 are independently selected from H, alkyl, aryl or a heterocyclic moiety;
• Y is selected from M, MX, BRaRb and MRaRbRc,
• wherein M is selected from alkali, Zn, Mg, Sn and Si;
• X is selected from CI, Br and I;
• Ra, Rb and Rc are independently selected from X, H, C1-C2 alkyl, phenyl and alkoxy;
• and when Y is BRaRb, then Ra and Rb form bidentate alkoxy;
• and
• ii) a compound selected from (R′)2Zn, (R′)2CuLi, (R′)2Cu(CN)Li2, R′R″CuLi or R′R″Cu(CN)Li2,
• wherein R′ is a group of formula V with R1 and R2 having the same structures as defined above, and
• R″ is a heteroaryl group,
• in an inert solvent, optionally in the presence of a promoter, to obtain compound of formula VI:
• (b) oxidative cleavage of the aliphatic carbon-carbon double bond of the obtained compound of formula VI and optionally isolating intermediate of formula VII;
• (c) dehydration of intermediate of formula VII;
• and
• (d) isolation of compound of formula I.